Normal rates of whole-body fat oxidation and gluconeogenesis after overnight fasting and moderate-intensity exercise in patients with medium-chain acyl-CoA dehydrogenase deficiency

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• 作者：Hidde H. Huidekoper ; Mari?tte T. Ackermans…
• 刊名：Journal of Inherited Metabolic Disease
• 出版年：2013
• 出版时间：September 2013
• 年：2013
• 卷：36
• 期：5
• 页码：831-840
• 全文大小：229KB
• 参考文献：1. Ackermans MT, Pereira Arias AM, Bisschop PH, Endert E, Sauerwein HP, Romijn JA (2001) The quantification of gluconeogenesis in healthy men by ²H₂O and [2-¹³C]glycerol yields different results: rates of gluconeogenesis in healthy men measured with ²H₂O are higher than those measured with [2-¹³C]glycerol. J Clin Endocrinol Metab 86:2220-226 CrossRef
  2. Bergstrom J (1975) Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest 35:609-16 CrossRef
  3. Boden G (2004) Gluconeogenesis and glycogenolysis in health and diabetes. J Investig Med 52:375-78 CrossRef
  4. Derks TG, Reijngoud DJ, Waterham HR et al (2006) The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome. J Pediatr 148:665-70 CrossRef
  5. Derks TG, van Spronsen FJ, Rake JP, van der Hilst CS, Span MM, Smit GP (2007) Safe and unsafe duration of fasting for children with MCAD deficiency. Eur J Pediatr 166:5-1 CrossRef
  6. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS (2007) Regulation of lipolysis in adipocytes. Annu Rev Nutr 27:79-01 CrossRef
  7. Frayn KN (1983) Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol 55:628-34
  8. Griffith AD, Cyr DM, Egan SG, Tremblay GC (1989) Inhibition of pyruvate carboxylase by sequestration of coenzyme A with sodium benzoate. Arch Biochem Biophys 269:201-07 CrossRef
  9. Halldin MU, Forslund A, von Dobeln U, Eklund C, Gustafsson J (2007) Increased lipolysis in LCHAD deficiency. J Inherit Metab Dis 30:39-6 CrossRef
  10. Heales SJ, Thompson GN, Massoud AF, Rahman S, Halliday D, Leonard JV (1994) Production and disposal of medium-chain fatty acids in children with medium-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis 17:74-0 CrossRef
  11. Huidekoper HH, Schneider J, Westphal T, Vaz FM, Duran M, Wijburg FA (2006) Prolonged moderate-intensity exercise without and with L-carnitine supplementation in patients with MCAD deficiency. J Inherit Metab Dis 29:631-36 CrossRef
  12. Jeukendrup AE, Raben A, Gijsen A et al (1999) Glucose kinetics during prolonged exercise in highly trained human subjects: effect of glucose ingestion. J Physiol 515(Pt 2):579-89 CrossRef
  13. Kean EA, Pogson CI (1979) Inhibition of gluconeogenesis in isolated rat liver cells by methylenecyclopropylpyruvate (ketohypoglycin). Biochem J 182:789-96
  14. Koopman R, Schaart G, Hesselink MK (2001) Optimisation of oil red O staining permits combination with immunofluorescence and automated quantification of lipids. Histochem Cell Biol 116:63-8
  15. Kuipers H, Verstappen FT, Keizer HA, Geurten P, van Kranenburg G (1985) Variability of aerobic performance in the laboratory and its physiologic correlates. Int J Sports Med 6:197-01 CrossRef
  16. Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC (1996) Contributions of gluconeogenesis to glucose production in the fasted state. J Clin Invest 98:378-85 CrossRef
  17. Orngreen MC, Norgaard MG, Sacchetti M, van Engelen BG, Vissing J (2004) Fuel utilization in patients with very long-chain acyl-coa dehydrogenase deficiency. Ann Neurol 56:279-83 CrossRef
  18. Orngreen MC, Duno M, Ejstrup R et al (2005) Fuel utilization in subjects with carnitine palmitoyltransferase 2 gene mutations. Ann Neurol 57:60-6 CrossRef
  19. Peronnet F, Massicotte D (1991) Table of nonprotein respiratory quotient: an update. Can J Sport Sci 16:23-9
  20. Petersen KF, Shulman GI (2006) Etiology of insulin resistance. Am J Med 119:S10–S16 CrossRef
  21. Previs SF, Hazey JW, Diraison F, Beylot M, David F, Brunengraber H (1996) Assay of the deuterium enrichment of water via acetylene. J Mass Spectrom 31:639-42 CrossRef
  22. Reinauer H, Gries FA, Hubinger A, Knode O, Severing K, Susanto F (1990) Determination of glucose turnover and glucose oxidation rates in man with stable isotope tracers. J Clin Chem Clin Biochem 28:505-11
  23. Roe CR, Ding J (2001) Mitochondrial fatty acid oxidation disorders. In: Scriver CR, Beaudet AL et al (eds) The metabolic and molecular bases of inherited disease. McGraw Hill, New York, pp 2297-326
  24. Romijn JA, Coyle EF, Sidossis LS et al (1993) Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol 265:E380–E391
  25. Rosenblatt J, Wolfe RR (1988) Calculation of substrate flux using stable isotopes. Am J Physiol 254:E526–E531
  26. Ruiter AF, Ackermans MT, Endert E (2001) Simultaneous gas chromatographic determination of concentration and isotopic enrichment of fatty acids in human plasma using flame ionization and mass spectrometric detection. J Chromatogr B: Biomed Sci Appl 759:169-74 CrossRef
  27. Saudubray JM, Martin D, de Lonlay P et al (1999) Recognition and management of fatty acid oxidation defects: a series of 107 patients. J Inherit Metab Dis 22:488-02 CrossRef
  28. Schaart G, Hesselink RP, Keizer HA, van Kranenburg G, Drost MR, Hesselink MK (2004) A modified PAS stain combined with immunofluorescence for quantitative analyses of glycogen in muscle sections. Histochem Cell Biol 122:161-69 CrossRef
  29. Sidossis LS, Coggan AR, Gastaldelli A, Wolfe RR (1995) A new correction factor for use in tracer estimations of plasma fatty acid oxidation. Am J Physiol 269:E649–E656
  30. Steele R (1959) Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci 82:420-30 CrossRef
  31. Tanaka K, Gregersen N, Ribes A et al (1997) A survey of the newborn populations in Belgium, Germany, Poland, Czech Republic, Hungary, Bulgaria, Spain, Turkey, and Japan for the G985 variant allele with haplotype analysis at the medium chain Acyl-CoA dehydrogenase gene locus: clinical and evolutionary consideration. Pediatr Res 41:201-09 CrossRef
  32. van Loon LJ, Greenhaff PL, Constantin-Teodosiu D, Saris WH, Wagenmakers AJ (2001) The effects of increasing exercise intensity on muscle fuel utilisation in humans. J Physiol 536:295-04 CrossRef
  33. van Loon LJ, Koopman R, Schrauwen P, Stegen J, Wagenmakers AJ (2003) The use of the [1,2-¹³C]acetate recovery factor in metabolic research. Eur J Appl Physiol 89:377-83 CrossRef
  34. van Vlies N, Tian L, Overmars H et al (2005) Characterization of carnitine and fatty acid metabolism in the long-chain acyl-CoA dehydrogenase-deficient mouse. Biochem J 387:185-93 CrossRef
  35. Wanders RJ, Schutgens RB, Zoeters PH (1988) 3-Hydroxy-3-methylglutaryl-CoA lyase in human skin fibroblasts: study of its properties and deficient activity in 3-hydroxy-3-methylglutaric aciduria patients using a simple spectrophotometric method. Clin Chim Acta 171:95-01 CrossRef
  36. Wang SS, Fernhoff PM, Hannon WH, Khoury MJ (1999) Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review. Genet Med 1:332-39 CrossRef
  37. Zhang D, Liu ZX, Choi CS et al (2007) Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proc Natl Acad Sci U S A 104:17075-7080 CrossRef
  
• 作者单位：Hidde H. Huidekoper (1)
  Mari?tte T. Ackermans (2)
  René Koopman (4)
  Luc J. C. van Loon (4)
  Hans P. Sauerwein (3)
  Frits A. Wijburg (1) (5)
  
  1. Department of Pediatrics, University of Amsterdam, Amsterdam, The Netherlands
  2. Department of Clinical Chemistry, Laboratory for Endocrinology and Radiochemistry, University of Amsterdam, Amsterdam, The Netherlands
  4. Department of Human Movement Sciences, Maastricht University Medical Centre, Maastricht, The Netherlands
  3. Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  5. Department of Pediatrics (H7-270), Academic Medical Center, University Hospital of Amsterdam, PO-box 22660, 1100 DD, Amsterdam, The Netherlands
  
• ISSN：1573-2665

文摘

Background Impairments in gluconeogenesis have been implicated in the pathophysiology of fasting hypoglycemia in medium-chain acyl-CoA dehydrogenase deficiency. However, whole body glucose and fat metabolism have never been studied in vivo. Methods Stable isotope methodology was applied to compare fat and glucose metabolism between four adult patients with MCADD and four matched controls both at rest and during 1.5?h of moderate-intensity exercise. Additionally, intramyocellular lipid and glycogen content and intramyocellular acylcarnitines were assessed in muscle biopsies collected prior to and immediately after cessation of exercise. Results At rest, plasma FFA turnover was significantly higher in patients with MCADD, whereas the plasma FFA concentrations did not differ between patients and controls. Blood glucose kinetics did not differ between groups both at rest and during exercise. Palmitate and FFA turnover, total fat and carbohydrate oxidation rates, the use of muscle glycogen and muscle derived triglycerides during exercise did not differ between patients and controls. Plasma FFA oxidation rates were significantly lower in patients at the latter stages of exercise. Free carnitine levels in muscle were lower in patients, whereas no differences were detected in muscle acetylcarnitine levels. Conclusions Whole-body or skeletal muscle glucose and fat metabolism were not impaired in adult patients with MCADD. This implies that MCADD is not rate limiting for energy production under the conditions studied. In addition, patients with MCADD have a higher FFA turnover rate after overnight fasting, which may stimulate ectopic lipid deposition and, as such, make them more susceptible for developing insulin resistance.